Soluble and particulate guanylate cyclase from rat and beef liver and heart will be purified to homogeneity in sufficient quantity to perform a variety of physicochemical and kinetic studies and prepare antibodies to holoenzyme and its subunits. Effects of free radicals such as hydroxyl radical and nitric oxide as well as other agents such as nitroprusside, fatty acids and peroxides will be examined with regard to guanylate cyclase activation and alteration of the physicochemical and kinetic properties of the enzyme. Antibodies to guanylate cyclase and its subunits will be used to examine antigenic similarities of soluble and/or particulate forms of inactive and active guanylate cyclase and adenylate cyclase in liver, heart and other tissues. The effects of cyclic GMP, cyclic AMP and various drugs and hormones that alter the levels of these cyclic nucleotides will be examined for their effects on redox systems, pyridine nucleotides, free radical formation and lipid peroxidation to test a new hypothesis regarding possible functions of cyclic GMP in tissues. The effects of phospholipase and E. Coli heat stable enterotoxin on guanylate cyclase will also be examined as possible models for hormonal regulation of the enzyme. Cyclic nucleotides in urine plasma and other clinical specimens will continue to be used to diagnose and/or evaluate the pathophysiology and therapy of some disorders.